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VOLUME 9 NUMBER 3 • SEPTEMBER 2012
REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
aged 20–29 years had the metabolic syndrome, compared with
fewer than 10% in the general US population.
5
The implication of
this finding is that healthcare professionals need to pay attention
to cardiovascular risk-factor management in people with severe
mental illness from the point of diagnosis rather than waiting until
they reach the age of 40 years, when they would be eligible for
screening under the NHS Health Check programme.
The worldwide prevalence of obesity has increased dramatically
over the last three decades, largely driven by changes in diet and
physical activity. These demographic changes appear to have
affected people with severe mental illness to a greater extent than
the general population, as studies that pre-date the 1980s did not
consistently report that obesity was commoner in those with severe
mental illness.
6
By contrast, more recent studies have reported
obesity rates that are approximately doubled in people with
schizophrenia or bipolar illness. Body composition is also altered
in people with severe mental illness: higher waist-to-hip ratios and
increased visceral fat have been found even at first presentation
of psychosis. Other studies have not replicated these findings, but
note marked weight gain and increasing girth during treatment
with antipsychotic medication.
6
It is estimated that between 10% and 15% of people with
severe mental illness have diabetes.
4
Type 1 diabetes is not increased
and so the 2–3-fold excess is explained by an increase in type 2
diabetes. It is well recognised that approximately 25% of cases of
type 2 diabetes are undiagnosed in the general population but this
situation is exaggerated in people with severe mental illness, among
whom as many as 70% of cases are undiagnosed. This may reflect
a reluctance of people with severe mental illness to volunteer their
symptoms and the overlap between some symptoms of diabetes
and mental illness, which may lead to reduced screening in people
with severe mental illness.
The major lipid abnormalities seen in people with severe mental
illness are lower levels of high-density lipoprotein (HDL) cholesterol
and hypertriglyceridaemia, although not all studies have shown
these abnormalities.
7
Overall, dyslipidaemia is reported in 25–69% of people with
severe mental illness.
Although some studies have reported increased rates of
hypertension, this again is not a universal finding, probably reflecting
the diverse action of antipsychotics on blood pressure.
7
Smoking rates
are high in people with severe mental illness, affecting 50–80%.
Antipsychotic medication and cardiovascular disease
There are concerns that antipsychotics contribute to cardiovascular
risk by inducing weight gain and worsening lipid profile and blood
glucose. Weight gain is a well-recognised side effect, affecting
between 15 and 72% of patients.
6
Although no antipsychotic can be viewed as weight-neutral,
the risk of weight gain differs between antipsychotics: mean
weight gain is highest with clozapine and olanzapine, there is an
intermediate risk of weight gain with quetiapine and risperidone
whereas aripiprazole, amisulpride and ziprasidone have little effect
on weight. Some first-generation antipsychotics (FGAs), such as
chlorpromazine, and other psychotropic medication, such as the
antidepressant mirtazapine, are also associated with a high risk
of inducing weight gain. Although choice of antipsychotic may
be used to predict weight gain, there is marked interindividual
variation in treatment-induced weight change. Other factors
associated with weight gain are younger age, lower initial body
mass index, family history of obesity, concomitant cannabis use
and a tendency to overeat at times of stress.
6
The best predictor of
long-term weight gain is weight change in the first 4–6 weeks of
treatment, emphasising the need for regular weight measurement
during the early phase of treatment.
The relationship between antipsychotics and diabetes is complex
because of the long natural history of diabetes and the potential
confounding effects of other diabetes risk factors in people with
severe mental illness.
8
Both genetic and lifestyle factors, such as
imprudent diet and physical inactivity, may contribute to the increased
prevalence of diabetes in people with severe mental illness.
Nevertheless, there are case reports of drug-induced diabetes
and diabetic ketoacidosis with each of the second-generation
antipsychotics; some of these report that diabetes enters remission
when the drug is stopped. A large number of pharmaco-
epidemiological studies have indicated that people receiving
antipsychotics have a higher prevalence of diabetes and that people
receiving second-generation drugs have a small but increased risk
of diabetes compared with those receiving first-generation drugs.
By contrast, randomised controlled trials have not demonstrated
a difference in treatment-emergent diabetes between different
antipsychotics or placebo, suggesting that the reasons why
individuals with severe mental illness develop diabetes are much
more likely to reflect their genetics, lifestyle and illness than their
treatment. On the other hand, small increases in blood glucose
have been reported, particularly with olanzapine and clozapine,
which, if persistent over a lifetime, may translate into meaningful
differences in the rates of diabetes.
Antipsychotic treatment is also associated with increases in low-
density lipoprotein (LDL) cholesterol and triglycerides and decreased
HDL cholesterol. Again, there are differences between drugs, with
greater changes generally being seen with those drugs that induce
the most weight gain. There may also be other direct mechanisms as
hypertriglyceridaemia may occur despite only modest weight gain.
The effect of antipsychotics on blood pressure is variable: although
weight gain may lead to increased blood pressure, this may be offset
by the adrenergic blockade seen with antipsychotics.
7
Although it appears that antipsychotics have an adverse effect
on several individual cardiovascular risk factors, it is important to
appreciate that this may differ from their effect on cardiovascular
events and mortality. A large UK study of more than 46 000 people
found that while exposure to first-generation antipsychotics,
particularly in high doses, was associated with excess cardiovascular
mortality, this increase was not seen in people receiving second-
generation antipsychotics.
3
Similarly, in a large Finnish study of
66 881
people with schizophrenia, total mortality was lowest in
individuals receiving clozapine and olanzapine, with no difference
in cardiovascular mortality between drugs.
9
These studies are both
observational and therefore there may be other explanations or
confounders underlying the results, but nevertheless the data are
reassuring.
Screening for diabetes and cardiovascular risk factors
The increased prevalence of cardiovascular disease and its
modifiable risk factors in people with severe mental illness provides
a strong imperative to screen for diabetes and other cardiovascular
risk factors. Although the case for screening does not fulfil all of the
criteria laid down by the National Screening Committee, screening
